Treatment of Experimental Ascending Escherichia coli Pyelonephritis with Ceftriaxone Alone and in Combination with Gentamicin

We have tested the effectiveness of several antibiotic regimens, using a rat model of Escherichia coli experimental pyelonephritis that mimics the conditions of severe renal infections in man because the infection is acquired by the ascending route. We found that ceftriaxone, when given for 5 days to rats with severe exudative pyelonephritis, was as effective as the combination ceftriaxone + gentamicin or the reference combination ampicillin + gentamicin. This effectiveness in vivo of the antibiotic alone was achieved despite a marked synergism between the combinations of antibiotics in vitro. This observation suggests that a new and extremely active cephalosporin is as effective in vivo when used alone as when given in combination with an aminoglucoside and provides rationale for testing the use of single antibiotic therapy for clinical situations for which combinations of antibiotics are currently recommended.